<<

. 5
( 45 .)



>>

Cerebellar mcoordmatton 0 8535 06111
Akinetic muttsm 0.726 1 0.7778
Muscle wasting 0.1656 0.8333
Characteristic electroencephalogram 0.4552 1.oooo


procedure achieved a high rate of diagnosis, with 52 out of 55 autopsy-verified
cases revealing sponglform change (14). Against this has to be weighed the
attendant risks of accidental transmission to other patients and staff (56). In
28 de Silva
Table 5
Summary of the Human Spongiform Encephalopathies
Sporadic CJD
Classical Presentmg with cogmttve dysfimctron alone (40%)
Presenting with cerebellar dysfunctton alone (30%)
Presenting with cognmve and cerebellar dysfunction ( 10%)
Other presenting features (10%)
Hetdenham varrant Presenting with occtpttal blindness (10%)
Brownell-Oppenheimer variant Progressive cerebellar syndrome (rare)
Panencephalopathx (Rare)
Familial CJD
Phenotypes linked with 19 separate PRNP open reading frame mutattons, including
Phenotype resembling sporadtc CJD,
Gerstmann-Straussler syndrome,
“Telencephahc” CJD,
Fatal famthal insomnia,
Famtltal CJD with spastic paraparests, and
Phenotype resembling Alzhermer disease
However, there 1s considerable overlap and the phenotypes are not mutation-spectfic
latrogenic CJD
Central maculation Resembles sporadic CJD
Peripheral moculatton Progressive cerebellar syndrome
Kuru


famthal cases PRNP genome analysis clearly is Invaluable. Since a family his-
tory of neurodegeneratton is not available always; this should perhaps be con-
stdered routinely m suspect CJD cases, espectally in cases presenting at a young
age and appearing to run a long course. The role of the common polymorphtsm
at codon 129 m the diagnoses of CJD 1s more uncertain. Although most spo-
radic CJD cases are likely to be methionme homozygous at this site (57,58),
approx 39% of the normal Caucasian British populatton are also of the same
genotype (59). Extrapolating from our own data (based on the genotypes of 68
sporadic CJD cases, and 16 non-CJD cases), the relative sensittvtty and spect-
fictty of methtonme homozygostty at codon 129 for the dtagnosts of CJD are
0.8382 and 0.5000, respecttvely.
CJD is finally an incurable disease. Despite their early promise, both
Amanttdme and Amphotericm have little or no effect on the course of illness
(60,62). However, sulfated glycosammoglycans (62) and even antisense ohgo-
nucleotldes may offer hope in the future as therapies At present, patients only
can be treated supporttvely. Depending on the certainty of the diagnosis and
the relatives™ wishes, hydration and arttficial feeding may be instituted. If the
patient is perceived to be m pain, opiate analgesics should be administered.
Myoclonus (which can be particularly distressing for relatives to watch) usu-
ally responds to Clonazepam or Valproate.

Note Added in Proof
Zerr et al. have recently reported elevated neuron-specific enolase concentra-
tions m the CSF of patients with CJD (63). The enzyme is known to be elevated in
CSF in a variety of neurological disorders, and may lack diagnostic specificity.

Acknowledgments
The author is grateful to R. Will for reviewing the text. The clmlcal data
presented was collected by R. Will, T. Esmonde, M. Zeidler, and the author.
The UK National Surveillance Unit receives funding from the Department of
Health and the Scottish Home and Health Department.

References
1 Creutzfeldt, H. G. (1920) Uber eine elgenartlge herdformlge Erkrankung des
Zentralnervensystems. Ze&whr˜jIjiir dzegesamte Neurologle und Psychlatrle 57, l-l 8.
2 Jakob, A (192 1) Uber eme der multlplen Sklerose khmsch nahestehende Erkrankung
des Zentralnervensystems (spastische Pseudosklerose) mit bemerkenswertem
anatomlschem Befunde Mltteilung emes vierten Falles Med Mm. 17, 372-376
3 Jakob, A (1923) Die Extrapyramldalen Erkrankungen, Springer, Berlin, pp 2 1%245
4 Jones, D P. and Nevm, S (1954) Rapldly progressive cerebral degeneration (sub-
acute vascular encephalopathy) with mental disorder, focal disturbances, and
myolomc epilepsy J Neurol Neurosurg Psychzat 17, 148-159
5. Nevm, S., McMenemey, W H , Behrman, S , and Jones, D P (1960) Subacute
spongiform encephalopathy-a subacute form of encephalopathy attributable to
vascular dysfunction (sponglform cerebral atrophy) Brazn 83, 5 19-564.
6. Heidenhain, A. (1929) Klmische und Anatomische Untersuchungen uber eme
elgenartlge Erkrankung des Zentralnervensystems Irn Praesemum Z Ges Neural
Psychrat 118,49
7. Meyer, A, Leigh, D , and Bagg, C. E (1954) A rare presemle dementia associ-
ated with cortical blindness (Hetdenham™s syndrome) J Neural. Neurosurg
Psychlat 17, 129-133
8. Brownell, B. and Oppenheimer, D. R (1965) An ataxlc form of subacute presemle
pohoencephalopathy (Creutzfeldt-Jakob disease) J Neural Neurosurg Psychlat
28,350-36 1
9 GaJdusek, D. C and Zlgas, V (1959) Kuru. Climcal, pathological and epldemlo-
logical study of an acute progressive degenerative disease of the central nervous
system among natives of the Eastern Highlands of New Guinea. Am J Med 26,
442-469
10. Simpson, D. A., Lander, H., and Robson, H. N. (1959) Observations on kuru: II
Chnical features Australas Ann Med 8, 8-1.5
30 de Sliva

11 Hornabrook, R W (1979) Kuru and chntcal neurology, m Slow Transmtsszble
Dzseases ofthe Nervous System, vol 1 (Prusmer, S B and Hadlow, W. J , eds ),
Academic, New York, pp 37-66
12 Masters, C L., Harris, J 0, GaJdusek, C., Gibbs, C J , Jr, Bernoulh, C., and
Asher, D. M ( 1979) Creutzfeldt-Jakob disease* patterns of worldwide occurrence
and the significance of famthal and sporadic clustering Ann Neurol 5, 177-I 88
13 Brown, P , Cathala, F , Castaigne, P , and GaJdusek, D C (1986) Creutzfeldt-
Jakob disease. chmcal analysis of a consecutive series of 230 neuropathologically
verified cases Ann Neurol 20, 597602.
14 Brown, P , Gibbs, C J , Jr, Rodgers-Johnson, P , Asher, D M , Sulima, M P ,
Bacote, A , et al (1994) Human spongiform encephalopathy the National Insti-
tutes of Health series of 300 cases of expertmentally transmitted disease Ann
Neurol 355 13-529
15 Cathala, F and Baron, H. (1987) Clmical aspects of Creutzfeldt-Jakob disease, m
Prtons Novel infecttous Pathogens Caustng Scrapte and Creutzfeldt-Jakob Dts-
ease (Prusmer, S B and McKinley, M P., eds ), Academic, San Diego, pp 467-509
16 Knight, R (1987) Transmissible dementia. clmtcal aspects, m Degeneratzve Neu-
rologtcal Disease tn the Elderly (Grtffiths, R A and McCarthy, S T , eds ),
Wright, Bristol, pp 109-l 18
17 Will, R G and Matthews, W B (1984) A retrospective study of Creutzfeldt-
Jakob disease m England and Wales 1970-79 I clmical features J New-01
Neurosurg Psychrat 47, 134-140
18. Brown, P., Rodgers-Johnson, P., Cathala, F , Gibbs, C J , Jr., and GaJdusek, D C
(1984) Creutzfeldt-Jakob disease of long duration: clmicopathological character-
istics, transmisstbihty, and differential diagnosis Ann Neurol 16,295-304
19 McNaughton, H and Will, R (1994) Creutzfeldt-Jakob disease presenting as
stroke. an analysis of 30 cases. Ann Neurol 36,3 13.
20 Salazar, A M , Masters, C L., Gajdusek, D. C , and Gibbs, C J., Jr (1983) Syn-
dromes of amyotrophic lateral sclerosis and dementia relation to transmissible
Creutzfeldt-Jakob disease. Ann Neurol 14(l), 17-26
21 Neary, D (1990) Non Alzhetmer™s disease forms of cerebral atrophy J Neurol
Neurosurg Psychtat 53,92993 1
22 Kitagawa, Y , Gotoh, F , Koto, A., Ebthara, S., Okayasu, H , Ishu, T , et al (1983)
Creutzfeldt-Jakob disease a case with extensive white matter degeneration and
optic atrophy J Neurol 229,97-l 01.
23 Macchi, G , Abbamondi, A L , Di Trapam, G , and Sbrtccoh, A (1984) On the
white matter lesions of Creutzfeldt-Jakob disease Can a new subentity be
recogmsed m man? J Neurol SCI 63, 197-206
24 Kawata, A., Suga, M , Oda, M , Hayashi, H , and Tanabe, H (1992) Creutzfeldt-
Jakob disease with congophihc km-u plaques* CT and pathological tindmgs of the
cerebral white matter J Neurol Neurosurg Psychtat 55, 849-85 1.
25. Gerstmann, J (1928) Uber em noch mcht beschriebenes Reflexphanomen bei
emer Erkrankung des zerebellaren Systems, Weiner Medtzintsche Wochenschrtft
78,906-908.
Human Spongiform Encephalopathy 37

26 Gerstmann, J., Straussler, E , and Scheinker, I. (1936) Uber eme ergenartige
heredttar-famlhare Erkrankung des Zentralnervensystems Zuglerch em Bertrag
zur Frage des vorzemgen lokalen Alterns. ZeltschriftSur Neurologle 154,736-162.
Masters, C L , GaJdusek, D C., and Grbbs, C. J., Jr. (1981) Creutzfeldt-Jakob
27
disease vnus isolations from the Gerstmann-Strlussler syndrome with an analysis
of the various forms of amyloid plaque depositton m the vnus-induced spongtform
encephalopathies. Brain 104,559-588.
Hsiao, K., Baker, H. F , Crow, T. J , Poulter, M , Owen, F , Terwtlhger, J D , et
28
al (1989) Linkage of a pnon protem missense variant to Gerstmann-Straussler
syndrome Nature 338,342-345
Kretzschmar, H. A., Honold, G., Sertelberger, F., Feucht, M , Wessely, P , et al
29
(1991) Prron protein mutation m famrly first reported by Gerstmann, Straussler,
and Schemker. Lancet 337, I 160.
Knschbaum, W. R. (1924) Zwei ergenartige Erkrankungen des Zentralnervensystems
30
nach Art der spastischen Pseudosclerose (Jakob). Z Ges. Neural Psychiat 92,
175-202
31 Brown, P , Cervenakova, L., Boellaard, J. W., Stavrou, D , Goldfarb, L., and
Gajdusek, D C (1994) Identification of a PRNP genemutation m Jakob™s orrgmal
Creutzfeldt-Jakob disease family. Lancet 344, 130-I 3 1.
32 Brown, P , Goldfarb, L G , Brown, W T , Goldgaber, D , Rubenstem, R ,
Kascsak, R J., et al (1991) Clmrcal and molecular genetic study of a large
German kindred with Gerstmann-Straussler-Scheinker syndrome Neurology 41,
375-379.
33 Barbanti, P , Fabbrmr, G , Salvatore, M., Petraroli, R., Pocchtarr, M , Macchr, G ,
et al (1994) Phenotyprc heterogeneity m Gerstmann-Straussler-Schemker syn-
drome with codon 102 mutation of the prion protein gene is not related to codon
129 polymorphism. Ann Neural 36,309
Ghetti, B., Taghavim, F., Hsiao, K., Dlouhy, S. R., Yee, R. D., Graccone, G., et al.
34
(1992) Indiana variant of Gerstmann-Straussler-Schemker dtsease, m Prron Du-
eases of Humans and Animals (Prusmer, S. B., Collmge, J Powell, J , and
Anderton, B., eds.), Ellis Horwood, London, pp 154-167
Hstao, K. K., Cass, C., Schellenberg, G. D.,Bnd,T., Devme-Gage, E , Wismiewski,
35
H , et al (199 1) A priori protein variant in a family with the telencephalic form of
Gerstmann-Straussler-Scheinker syndrome. Neurology 41,681-684.
Chapman, J , Brown, P , Goldfarb, L. G., Arlazoroff, A., Gajdusek, D. C., and
36
Korczyn, A. D. (1993) Climcal heterogeneity and unusual presentations of
Creutzfeldt-Jakob disease m Jewish patients with the PRNP codon 200 mutatron
J. Neural Neurosurg Psychzat. 56, 1109-l 112.
Medort, R., Trrtschler, H J., LeBlanc, A., Viliare, F., Manetto, V , Chen, H Y , et
37
al. (1992) Fatal famihal msomma, a prion disease with a mutation at codon 178 of
the prron protein gene. N Engl. J Med. 326,444-449.
Lugaresi, E , Medori, R., Montagna, P., Baruzzi, A., Cortelli, P., Lugaresi, A., et
38
al. (1986) Fatal famthal insomnia and dysautonomra with selective degeneration
of thalamic nuclei N Engl J Med 315(16), 997-1003.
32 de Srlva
39, Collmge, J , Brown, J , Hardy, J., Mullan, M., Rossor, M. N , Baker, H , et al
(1992) Inherited prton disease with 144 base pair gene insertion 2 Clmical and
pathological features Brazn 115, 687-7 10
40 La Spada, A R , Paulson, H L and Ftschbeck, K H (1994) Trmucleottde repeat
expansion m neurologtcal dtsease Ann Neural 36,8 14-82 1
41 Poulter, M , Baker, H F., Froth, C D., Leach, M , Lofthouse, R., Rtdley, R M , et
al (1992) Inherited prton disease with 144 base pair gene msertion 1 Genealogi-
cal and molecular studies. Bram 115, 675-685
42 Duchen, L W , Poulter, M , and Harding, A E (1993) Dementia associated with
a 216 base pair msertion m the priori protein gene Brazn 116, 555-567
43 Kitamoto, T , Amano, N , Terao, Y , Nakazato, Y , Isshiki, T , Mizutam, T., et al
(1993) A new inherited prton drsease (PrP-PlO5L mutation) showing spastic
paraparesis. Ann New-01 34,808-8 13.
44 Kttamoto, T , Iizuka, R , and Tateishi, J (1993) An amber mutation of priori pro-
tem m Gerstmann-Straussler syndrome with mutant PrP plaques Bzochem
Blophys Res Commun 192,525-53 1.
45 Brown, P (1988) The clinical neurology and eptdemiology of Creutzfeldt-Jakob
disease, with special reference to iatrogemc cases, m Novel Infectious Agents and the
Central Nervous System (Bock, G and Marsh, J , eds ), Wiley, Chichester, pp 3-23
46 Martinez-lage, J F , Poza, M , Sola, J , Tortosa, J G , Brown, P., Cervenhkovl,
L , et al (1994) Accidental transmisston of Creutzfeldt-Jakob disease by dural
cadaverrc grafts J Neurol. Neurosurg Psychlat 57, 109 l-1094
47 Tanaka, M., Iizuka, O., and Yuasa, T (1992) Hepatic dysfunction m Creutzfeldt-
Jakob disease Neurology 42, 1249
48 Tanaka, M (1993) Liver m Creutzfeldt-Jakob disease Neurology 43,457
49 Uchmo, A , Yoshinaga, M , Shiokawa, 0 , Hata, H., and Ohno, M (1991) Serial
MR imaging in Creutzfeldt-Jakob disease. Neuroradzology 33, 364-367
50 Milton, W J., Atlas, S W., Lava, E , and Mollman, J E (1991) Magnetic reso-
nance imaging of Creutzfeldt-Jakob disease. Ann New-01 29,438-440
51 Onofrj, M , Fulgente, T , Gambt, D , and Maccht, G (1993) Early MRI findmgs
m Creutzfeldt-Jakob disease J Neural 240,423426.
52 Graham, G D , Petroff, 0 A C , Blamire, A M , RaJkowska, G , Goldman-Rakic,
P., and Prichard, J W (1993) Proton magnetic resonance spectroscopy rn
Creutzfeldt-Jakob disease Neurology 43,2065-2068
53 Harrmgton, M. G , Merrtl, C R , Asher, D M , and GaJdusek, D C (1986)
Abnormal proteins m the cerebrospmal fluid of patients with Creutzfeldt-Jakob
disease N Engl J Med 315,279-283
54. Blisard, K S., Davis, L E., Harrmgton, M. G , Lovell, J K., Kornfeld, M , and
Berger, M L. (1990) Pre-mortem diagnosis of Creutzfeldt-Jakob disease by
detection of abnormal cerebrospmal fluid protems. J Neurol Scz 99,75-8 1
55. Esmonde, T. G and Will, R G (1992) Creutzfeldt-Jakob disease m Scotland and
Northern Ireland Scot Med J 37, 181-184.
56 Advisory Committee on Dangerous Pathogens (1994) Precautions for work with
human and ammal transmisstble spongiform encephalopathtes HMSO, London
Human Spongiform Encephalopathy 33

57. Palmer, M S , Dryden, A , Hughes, J. T , and Collmge, J. (1991) Homozygous
prton protein genotype predisposes to sporadtc Creutzfeldt-Jakob dtsease Nature
352,340-342
58. Laplanche, J -L , Delasnene-Laupretre, N , Brandel, J P , Chatelam, J , Beaudry,
P , Alperovitch, A , et al (I 994) Molecular genetics of prron diseases m France
Neurology 44,2347-235 I
59 Collmge, J and Palmer, M (1991) CJD drscrepancy Nature 353, 802
60. Sanders, W L and Dunn, T L (1973) Creutzfeldt-Jakob disease treated with
amantrdme A report of two cases J Neural Neurosurg Psychrat 36,58 l-584
61 Masullo, C., Macchi, G , XI, Y G , and Pocchiari, M (1992) Failure to ameliorate
Creutzfeldt-Jakob disease with amphoterictn B therapy. J Infect Dls 165,784--785
62 Caughey, B (1994) Scrapre-associated PrP accumulation and agent rephcation
analogues. Phzl Tram R Sot Lord B
effects of sulphated glycosammoglycan
343,399404
63. Zerr, I , Bodemer, M , Racker, S , Grosche, S , Poser, S , Kretzchmar, H A , and
Weber, T (1995) Cerebrospmal fluid concentration of neuron-specific enolase m
disease Lancet 345, 1609,161O
diagnosis of Creutzfeldt-Jakob
3
Neuropathological Diagnosis
of Human Prion Disease
Morphological Studies

James W. lronside


<<

. 5
( 45 .)



>>